TET1 regulates responses to house dust mite by altering chromatin accessibility, DNA methylation, and gene expression in airway epithelial cells.

Background: Previous studies have identified TET1 as a potential key regulator of genes linked to asthma. TET1 has been shown to transcriptionally respond to house dust mite extract, an allergen known to directly cause allergic asthma development, and regulate the expression of genes involved in asthma. How TET1 regulates expression of these genes, however, is unknown.

Factors Limiting the Translatability of Rodent Model-Based Intranasal Vaccine Research to Humans.

The intranasal route of vaccination presents an attractive alternative to parenteral routes and offers numerous advantages, such as the induction of both mucosal and systemic immunity, needle-free delivery, and increased patient compliance. Despite demonstrating promising results in preclinical studies, however, few intranasal vaccine candidates progress beyond early clinical trials. This discrepancy likely stems in part from the limited predictive value of rodent models, which are used frequently in intranasal vaccine research.

Single-Cell RNA-Seq Analysis Reveals Lung Epithelial Cell Type-Specific Responses to HDM and Regulation by Tet1.

Tet1 protects against house dust mite (HDM)-induced lung inflammation in mice and alters the lung methylome and transcriptome. In order to explore the role of Tet1 in individual lung epithelial cell types in HDM-induced inflammation, we established a model of HDM-induced lung inflammation in Tet1 knockout and littermate wild-type mice, then studied EpCAM lung epithelial cells using single-cell RNA-seq analysis. We identified eight EpCAM lung epithelial cell types, among which AT2 cells were the most abundant.

Long-term effects of wildfire smoke exposure during early life on the nasal epigenome in rhesus macaques.

Background: Wildfire smoke is responsible for around 20% of all particulate emissions in the U.S. and affects millions of people worldwide.

Intranasal vaccine: Factors to consider in research and development.

Most existing vaccines for human use are administered by needle-based injection. Administering vaccines needle-free intranasally has numerous advantages over by needle-based injection, but there are only a few intranasal vaccines that are currently approved for human use, and all of them are live attenuated influenza virus vaccines. Clearly, there are immunological as well as non-immunological challenges that prevent vaccine developers from choosing the intranasal route of administration.

Maintenance of Type IV Secretion Function During Helicobacter pylori Infection in Mice.

The type IV secretion system (T4SS) encoded on the pathogenicity island (PAI) secretes the CagA oncoprotein and other effectors into the gastric epithelium. During murine infection, T4SS function is lost in an immune-dependent manner, typically as a result of in-frame recombination in the middle repeat region of , though single nucleotide polymorphisms (SNPs) in or in other essential genes may also occur. Loss of T4SS function also occurs in gerbils, nonhuman primates, and humans, suggesting that it is biologically relevant and not simply an artifact of the murine model.

Identification of Pathogenicity Island Genes Associated with Loss of Type IV Secretion Function during Murine Infection with Helicobacter pylori.

Chronic colonization in animal models often leads to downregulation of the type IV secretion system (T4SS), typically by recombination in , which is an essential T4SS gene. However, 17 other pathogenicity island (PAI) genes, as well as some non-PAI genes, are also essential for T4SS function. To get a more complete picture of how regulates the T4SS during animal colonization, we examined in 534 mouse-passaged isolates that lost T4SS function, defined as a normalized interleukin-8 (IL-8) value of <0.

CagY-Dependent Regulation of Type IV Secretion in Helicobacter pylori Is Associated with Alterations in Integrin Binding.

Strains of that cause ulcer or gastric cancer typically express a type IV secretion system (T4SS) encoded by the pathogenicity island (PAI). CagY is an ortholog of VirB10 that, unlike other VirB10 orthologs, has a large middle repeat region (MRR) with extensive repetitive sequence motifs, which undergo CD4 T cell-dependent recombination during infection of mice. Recombination in the CagY MRR reduces T4SS function, diminishes the host inflammatory response, and enables the bacteria to colonize at a higher density.

CagY Is an Immune-Sensitive Regulator of the Helicobacter pylori Type IV Secretion System.

Background & Aims: Peptic ulcer disease and gastric cancer are caused most often by Helicobacter pylori strains that harbor the cag pathogenicity island, which encodes a type IV secretion system (T4SS) that injects the CagA oncoprotein into host cells. cagY is an essential gene in the T4SS and has an unusual DNA repeat structure that predicts in-frame insertions and deletions. These cagY recombination events typically lead to a reduction in T4SS function in mouse and primate models.

GAP Peptide Synthesis Design of New GAP Protecting Group: An Fmoc/tBu Synthesis of Thymopentin Free from Polymers, Chromatography and Recrystallization.

A novel method for Fmoc/tBu solution-phase peptide synthesis and the development of a new benzyl-type GAP protecting group is reported. This new GAP protecting group is utilized in place of a polymer support, facilitating C→N Fmoc peptide synthesis without chromatography, recrystallization, or polymer supports. The GAP group can be added and removed in high yield, and was used to synthesize over 1 gram of the immunostimulant, thymopentin, in high overall yield (83%) and purity (99%).